JPC SYSTEMIC PATHOLOGY
Signalment (JPC#3104060/WSC 08-09 4/3): A male New Zealand white rabbit.
HISTORY: Clinically normal animal, incidental finding at necropsy.
HISTOPATHOLOGIC DESCRIPTION: Liver: Multifocally bile ducts are tortuous and markedly ectatic (up to 4 mm), and often compress surrounding hepatic parenchyma. Ectatic ducts are expanded by hyperplastic biliary epithelium which forms branching papillary projections consisting of a single layer of columnar to cuboidal epithelial cells supported on a moderate fibrovascular stroma. Epithelial cells frequently have karyorrhectic, karyolytic, or pyknotic nuclei (necrosis). The hyperplasic biliary epithelium contains myriad developing coccidial life stages including many protozoal macrogametes and microgametes in various stages of gametogony. The macrogametes are round, 20-50 um in diameter, with a central nucleus, prominent nucleolus, and brightly eosinophilic 3-4 um diameter peripheral granules. The microgametes are round, 15-25 um in diameter, with peripheral lightly basophilic granules. Within the lumen and within epithelial cells there are moderate numbers of thin walled oocysts, gametocytes and cellular debris. The unsporulated oocysts are oval, 20-40 um in diameter with thick refractile walls that are often collapsed and contain lightly basophilic and eosinophilic, granular cytoplasm with a central eosinophilic nucleus. There are few intra or extracellular 10-30um meronts which contain numerous 1X4um crescent shaped merozoites. Ectatic bile ducts are surrounded by a narrow rim of fibrous connective tissue, moderate numbers of lymphocytes, fewer macrophages and plasma cells, and low numbers of degenerate neutrophils, along with increased clear space and ectatic lymphatics (edema). Diffusely, there is mild chronic portal and periportal lymphoplasmacytic inflammation.
MORPHOLOGIC DIAGNOSIS: Liver: Cholangitis, proliferative and lymphoplasmacytic, chronic, multifocal, severe, with ductular ectasia, fibrosis, and numerous intraepithelial macrogamonts, microgamonts and intraluminal oocysts, etiology consistent with Eimeria stiedae, New Zealand white rabbit (Oryctolagus cuniculus), lagomorph.
ETIOLOGY: Eimeria stiedae
ETIOLOGIC DIAGNOSIS: Hepatic eimeriosis
- Eimeria stiedae, a coccidian in the protozoal phylum Apicomplexa, parasitizes bile duct epithelium in both domestic and wild rabbits (Oryctolagus, Sylvilagus, and Lepus), and is an important cause of mortality in commercial rabbitries
- Eimeria Are divided into 5 overlapping groups based on pathogenicity:
- Non-pathogenic: coecicola
- Slightly pathogenic: perforance, E. exigua, E. vejdovskyi
- Mildly pathogenic or Pathogenic: media, E. magna, E. piriformis, E. irresidua
- Highly pathogenic intestinalis, E. flavescens
- Weanling rabbits are the most commonly affected
- Rabbits are usually co-infected with multiple Eimeria species
- Life cycle for each species of Eimeria (>1000) is host specific and direct
- E. stiedae oocysts are shed in feces > sporulate in 1 or more days > become infective > ingested sporozoites excyst in the intestine and invade the duodenal mucosa (systemic infection) > 1 or more asexual cycles depending on species
- Merozoites released from asexual stages eventually form sexual stages (male=microgamete, female=macrogamete) which unite to form oocysts > oocysts are released into the bile and shed in the feces
- Organism in regional mesenteric lymph nodes within 12 hours > migrate to liver in mononuclear cells via lymphatics
- Prepatent period is 15-18 days and oocysts may be shed in the feces for 7 weeks or more postexposure
- Schizogony in biliary epithelium induces bile duct necrosis and subsequent hyperplasia
- Severe portal fibrosis with nonsuppurative biliary hepatitis is common in chronic cases
- Severely affected livers have functional abnormalities attributable to the compression of liver parenchyma and bile duct obstruction
TYPICAL CLINICAL FINDINGS:
- Clinical disease most frequent during post-weaning period
- Four stages of disease:
- Initial metabolic dysfunction: Hepatocyte damage during schizogony
- Cholestatic stage: Elevated alanine transaminase (ALT), hyperbilirubinemia
- Second metabolic dysfunction stage: Hypoglycemia, hyperlipemia, and hypoproteinemia (hypoalbuminemia and hypergammaglobulinemia)
- Immunosupression: In heavily infected animals, individuals are unable to control the production of oocysts in the biliary system. The reason for this inability to control the infection is unknown, as no immune functions tests have been conducted in these animals
- Heavy infections may cause anorexia, a distended abdomen (enlarged liver and ascites), weight loss, and occasionally diarrhea and icterus
TYPICAL GROSS FINDINGS:
- Frequently thin and potbellied, and lack body fat reserves
- May be dark brown to green soiling in the perineal region
- Liver: Multiple, raised, linear bosselated (knob-like), yellowish-white to gray, circumscribed hepatic lesions 0.5-2cm in diameter (yellow to dark green inspissated material on cut section)
- Gall bladder is thickened and may contain green, viscous bile and debris
- Fibrosis may be present
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Marked dilation of bile ducts with epithelial hyperplasia forming papillary projections
- Large numbers of apicomplexan gametocytes, schizonts, and oocysts in affected ducts
- Extensive periportal fibrosis
- Mixed inflammatory cell infiltration in the periportal regions composed of lymphocytes, macrophages, and few eosinophils and neutrophils
- In chronic lesions, organisms may be sparse to absent in bile ducts with prominent periportal fibrosis
- Demonstration of the oocysts in the bile ducts
- In the dog, cat and pig, Isospora are more important pathogens; Eimeria sp. does affect adult pigs but rarely causes clinical disease
- Canine: Cystisospora canis
- Feline: Cystoisospora felis
- Rabbit: intestinalis, E. flavescens
- Crane: Eimeria gruis, E. reichenowi: These parasites develop in multiple organs or tissues in infected cranes, thus lacking the specificity of infection sites shown by other Eimeria sp. in spite of morphologic similarity
- Ophidian snakes: E. bitis in gallbladder and bile duct
- Ferret: E. furonis in gallbladder and bile duct
- Mink: E. hiepei in biliary ducts
- Chicken: E. tenella (cecum), E. necatrix, E. acervulina (small intestine)
- Goose: E. truncata (kidney tubules)
- Mouse: E. falciformis (small and large intestine)
- Guinea pig: E. caviae (large intestine)
- Cattle: E. zuernii, E. bovis (small and large intestine)
- Horse: E. leuckarti (small intestine)
- Sheep: E. ovinoidalis (terminal ileum), E. ahsata, E. ovina
- Turkey: E. meleagrimitis, E. adenoeides, E. gallopavonis, E. meleagridis
- Goat: E. ninakohlyakimovae (cecocolic area), E. christenseni, E. arloingi
- Przewalski’s Gazelle: E. jiangi, E. cagandzeeri
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- Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:297-300.
- Uzal FA, Platter BL, Hostetter JM. Alimentary System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St Louis, MO: Elsevier; 2016: 227-239.
- Gardiner CH, Fayer R, Dubey JP. An Atlas of Protozoan Parasites in Animal Tissues. 2nd ed., Washington, DC: Armed Forces Institute of Pathology;1998:20-30.
- MacDonald AM, Jardine CM, Reiman E, et al. High Prevalence of Mycoplasma and Eimeria Species in Free-Ranging Eastern Wild Turkeys (Meleagris gallopavo silvestris) in Ontario, Canada. J Wildl Dis. 2018; June 27: doi: 10.7589/2017-11-273. [Epub ahead of print].